Introduction
The present invention relates to purified drug resistant tumor cells, mutated polynucleotide sequences which confer drug resistance, an assay for detecting drug resistant tumor cells in mammals including human, reagents specific for PCR enhancement of mutant determinant polynucleotide sequences, and methods for treating patients afflicted with drug resistant tumor cells.
More particularly, this invention relates to an assay for detecting paclitaxel resistant tumor cells in humans using specific PCR primer polynucleotide sequences to selectively enhance and identify mutant genes from paclitaxel resistant tumor cells. This invention also relates to the specific polynucleotide primer sequences themselves, the specific mutant polynucleotide sequences and to methods for identifying paclitaxel resistant tumor cells and administering an effective amount of a secondary anti-tumor agent lethal to the identified paclitaxel resistant tumor cells.
Paclitaxel (Taxol), Taxotere and other paclitaxel-like drugs that are currently under development hold great promise for the treatment of human cancer. Paclitaxel has shown remarkable activity against breast and ovarian cancer, melanomas, non-small lung carcinoma, esophogeal cancer, Kaposi's sarcoma, and some hematological malignancies. It has been described as the most significant antitumor drug developed in the last several decades and will, without doubt, find widespread use in the treatment of cancer. However, as is true of virtually all cancer chemotherapeutic drugs, patients responsive to paclitaxel eventually relapse due to the emergence of drug resistant tumor cells.
Thus, there is a need in the art for methods to identify paclitaxel-resistant tumor cells, for agents that allow such identifications in a simple and cost effective way, and for methods for to treat patients with paclitaxel resistant tumor cells.